Exosomal microRNAs as a Biomarker in Panic Disorder and in Response to CBT

NCT04029740 | Unknown

• 1 other identifier: 0577-18-HMO
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Most studies focused on genomic differences and pursued differences in methylation patterns following CBT, but the findings were very limited in scope, especially when comparing responders and non-responders to CBT. In the currently proposed study, the investigators plan to go one step further and look for changes in exosomal microRNAs (miRs) from serum samples taken before and after CBT from Panic Disorder (PD) patients. Notably, miR changes show a much faster biological response than methylation patterns yet had never been used before in PD research. The primary benefit of this work will be in providing biological validation to psychological treatments. PD is a heavy public health burden, associated with significant market potential for both therapeutic and diagnostic uses.

Conditions

Panic Disorder

Outcome Measures

Primary Outcomes (1)

• Differntial expression of plasma exosomal microRNAs

  Exosomes are a type of extracellular vesicles of endocytic origin, used in signalling and cell to cell communication, by transferring proteins, lipids, and variety of RNAs between cells. miRs are short single-stranded RNA molecules that bind to complementary sequences of target mRNAs, causing inhibition of their translation and/or inducing target degradation and affecting brain functioning and mental processes. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).

  Pre and post treatment, up to 6 months apart.

Secondary Outcomes (7)

• Change in Panic Disorder Severity Scale (PDSS)

  Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.

• Change in Anxiety Sensitivity Index-3 (ASI-3)

  Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.

• Change in Mobility Inventory

  Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.

• Differntial expression of whole Blood short non-coding RNAs

  Pre and post treatment, up to 6 months apart.

• Change in the Five-Dimensional Curiosity Scale (DCS-5)

  Pre and post treatment, up to 6 months apart.

Study Arms (2)

Healthy controls

OTHER

40 Healthy controls matched on gender and age with no current psychopathology will have exosomal microRNAs measured twice over a 3 month period.

Other: No intervention

panic disorder receiving CBT

EXPERIMENTAL

40 adult patients diagnosed with primary panic disorder will have their exosomal microRNAs measured 2x over 3 months.

Behavioral: CBT- both internet and face to face

Interventions

CBT- both internet and face to face BEHAVIORAL

There are a few common psychotherapies for treating PD, with Cognitive Behavioral Therapy (CBT) as the most common. The most known type of CBT for treating PD consists of two major strategies: cognitive restructuring, and interoceptive and structured exposure to bodily sensations that have become associated with panic attacks (D H Barlow, 1997). The ICBT therapy is based on Barlow and Craske's (2007) protocol for treating PD with elaborations (Huppert \& Baker-Morissette, 2003). It includes six modules containing psychoeducation, cognitive restructuring, exposures, acceptance, and consolidation of gains and relapse prevention. The online modules include reading passages, worksheets, videos, and homework assignments. After completing each module, participants practice related skills and complete homework assignments. The treatment is up to 16 weeks long; participants are encouraged to complete the treatment within this time period, and reminders are sent to monitor their progress.

Also known as: Cognitive behavioral therapy for panic disorder

panic disorder receiving CBT

No intervention OTHER

Healthy controls will not receive any intervention.

Healthy controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Principal DSM-5 primary diagnosis of panic disorder and/or agoraphobia.
• Aged 18 years or older.
• PD duration of at least 3 months.
• If participant is on on medications for PD, the dosage has to remain constant for 3 months prior to the start of treatment and cannot be increased during treatment.
• The participant must have access to the internet and be willing to use it.

You may not qualify if:

• Substance abuse or dependence within the last 6 months.
• Active suicide potential within the last 6 months.
• Any current or history of psychosis or bipolar I disorder.
• Currently in weekly or biweekly psychotherapy.
• History of a complete course of panic focused CBT

Sponsors & Collaborators

• Hebrew University of Jerusalem: lead
• Hadassah Medical Organization: collaborator

Study Sites (1)

Hebrew University of Jerusalem

Jerusalem, 9190501, Israel

RECRUITING

Related Publications (11)

• Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Round JL, Ward DM, O'Connell RM. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun. 2015 Jun 18;6:7321. doi: 10.1038/ncomms8321.

  PMID: 26084661 BACKGROUND

• Andersson G, Cuijpers P, Carlbring P, Riper H, Hedman E. Guided Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review and meta-analysis. World Psychiatry. 2014 Oct;13(3):288-95. doi: 10.1002/wps.20151.

  PMID: 25273302 BACKGROUND

• Bekenstein U, Mishra N, Milikovsky DZ, Hanin G, Zelig D, Sheintuch L, Berson A, Greenberg DS, Friedman A, Soreq H. Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4996-E5005. doi: 10.1073/pnas.1701201114. Epub 2017 Jun 5.

  PMID: 28584127 BACKGROUND

• Barlow DH. Cognitive-behavioral therapy for panic disorder: current status. J Clin Psychiatry. 1997;58 Suppl 2:32-6; discussion 36-7.

  PMID: 9078992 BACKGROUND

• Fruhbeis C, Helmig S, Tug S, Simon P, Kramer-Albers EM. Physical exercise induces rapid release of small extracellular vesicles into the circulation. J Extracell Vesicles. 2015 Jul 2;4:28239. doi: 10.3402/jev.v4.28239. eCollection 2015.

  PMID: 26142461 BACKGROUND

• Huppert, J. D., & Baker-Morissette, S. L. (2003). Beyond the manual: The insider's guide to panic control treatment. Cognitive and Behavioral Practice, 10(1), 2-13.

  BACKGROUND

• Meunier J, Lemoine F, Soumillon M, Liechti A, Weier M, Guschanski K, Hu H, Khaitovich P, Kaessmann H. Birth and expression evolution of mammalian microRNA genes. Genome Res. 2013 Jan;23(1):34-45. doi: 10.1101/gr.140269.112. Epub 2012 Oct 3.

  PMID: 23034410 BACKGROUND

• Olthuis JV, Watt MC, Bailey K, Hayden JA, Stewart SH. Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults. Cochrane Database Syst Rev. 2016 Mar 12;3(3):CD011565. doi: 10.1002/14651858.CD011565.pub2.

  PMID: 26968204 BACKGROUND

• Roberts S, Lester KJ, Hudson JL, Rapee RM, Creswell C, Cooper PJ, Thirlwall KJ, Coleman JR, Breen G, Wong CC, Eley TC. Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders. Transl Psychiatry. 2014 Sep 16;4(9):e444. doi: 10.1038/tp.2014.83.

  PMID: 25226553 BACKGROUND

• Ziegler C, Richter J, Mahr M, Gajewska A, Schiele MA, Gehrmann A, Schmidt B, Lesch KP, Lang T, Helbig-Lang S, Pauli P, Kircher T, Reif A, Rief W, Vossbeck-Elsebusch AN, Arolt V, Wittchen HU, Hamm AO, Deckert J, Domschke K. MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy. Transl Psychiatry. 2016 Apr 5;6(4):e773. doi: 10.1038/tp.2016.41.

  PMID: 27045843 BACKGROUND

• Strawn JR, Mills JA, Sauley BA, Welge JA. The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric Anxiety Disorders: A Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2018 Apr;57(4):235-244.e2. doi: 10.1016/j.jaac.2018.01.015. Epub 2018 Feb 8.

  PMID: 29588049 BACKGROUND

MeSH Terms

Conditions

Panic Disorder

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Hermona Soreq, Professor

  Hebrew University of Jerusalem

  PRINCIPAL INVESTIGATOR

• Ronen Segman, Professor

  Hadassah Hebrew University Hospital

  PRINCIPAL INVESTIGATOR

• Salomon Israel, Professor

  Hebrew University of Jerusalem

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shani Vaknine, M.Sc student

CONTACT

+972543556299; shani.vaknine@mail.huji.ac.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: All patients will be treated with either internet or face to face CBT according to their preference. Circulating exosomal microRNAs will be measured pretreatment and post-treatment.

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: July 23, 2019
• Study Start: March 24, 2019
• Primary Completion: December 24, 2021
• Study Completion: December 24, 2021
• Last Updated: February 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available once the manuscript is submitted for publishing.

Locations

IL (1)